Cleft lip and/or palate (CLP) is a common birth defect occurring in about 1/500 to 1/2500 births. The majority of cases are nonsyndromic (NS) without other major birth defects or syndromes but NS CLP forms impose substantial health burden on both affected individuals and families. Early life complications include feeding problems and recurrent ear infections and increased long term risks may also occur for certain chronic conditions such as cancer, mental health conditions and mortality and for adverse socioeconomic outcomes. It is also anticipated that the health, social and economic outcomes of immediate family members may also be adversely affected. Yet much remains to be learned about the long term outcomes of CLP primarily due to the lack of appropriate and large-scale data sources to track cases and measure outcomes. Little is also known about the net effects of prenatal diagnosis of CLP, which is becoming increasingly common, on the health outcomes of affected children and their family members. Improved phenotypic characterization of CLP represents another priority research area that also provides a real prospect for improving the estimation of recurrence risks and counseling of affected families, increasing the power of genetic and gene-environment interaction studies and for early prediction of risks for adverse health and psychosocial outcomes. The proposed study addresses these priority areas, which represent CLP priority areas b, e, f, g, h in the RFA. The effects of NS CLP on long term health, health care utilization, and socioeconomic outcomes of affected individuals and their first degree relatives will be evaluated using a unique population registry system in Denmark which allows tracking about 8300 cases with NS CLP born starting 1936 and their first degree relatives through several health and socio-demographic registries of individual-level data on the whole population of Denmark. A random sample representing 5% of the Danish population will be selected with their first degree relatives as comparison groups. The study will also measure selected subphenotypes including Orbicularis Oris (OO) discontinuity, velopharyngeal incompetence (VPI), lip whorls, laterality and craniofacial dysmorphology in cases born with NS CLP in Iowa between 1996 and 2007 and identified through Iowa's birth defects registry and their first degree relatives as well as unaffected controls. Subphenotypic information will be used for recurrence risk estimation and will also be correlated with psychosocial outcomes. DNA samples will be obtained for gene-environment etiology studies that make use of the subphenotypic information. The study will also assess the effects of prenatal diagnosis on child and family outcomes in the samples from Iowa and measure parental preferences towards prenatal diagnosis. The study provides a real opportunity for adding significant scientific knowledge that can be directly translated into improving the outcomes of affected individuals and families and that may increase the chances for developing prevention strategies.This project aims at evaluating the long term health outcomes of cleft lip and palate and at identifying traits and characteristics that may be associated with this burdensome and common birth defect. The study results are highly relevant for identifying health care needs, improving care practices and developing strategies to prevent cleft lip and palate and/or reduce its associated adverse effects.